Any type of breast cancer not expressing genes of the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) is referred to as triple-negative breast cancer (TNBC). Accordingly, TNBCs do not respond to hormonal therapies or medicines targeting the ER, PR, or HER2. Systemic chemotherapy is therefore the only treatment option available today and prognoses remain poor. We report the discovery and characterization of N-(naphtho[1,2-b]furan-5-yl)benzenesulfonamides as selective inhibitors of TNBCs...

Oxidative stress can contribute to an acceleration of telomere erosion, leading to cellular senescence and aging. Increased investment in reproduction is known to accelerate senescence, generally resulting in reduced future reproductive potential and survival. To better understand the role played by oxidative status and telomere dynamics in the conflict between maintenance and reproduction, it is important to determine how these factors are related in parents and their offspring. We investigated the relationship between oxidative status and telomere measurements in pied flycatchers (Ficedula hypoleuca)...

Effect-Directed Analysis (EDA) is a commonly used approach for effect-based identification of endocrine disruptive chemicals in complex (environmental) mixtures. For routine toxicity assessment of e.g. water samples however, current EDA approaches are considered time consuming and laborious. We achieved faster EDA and identification, by downscaling of sensitive cell-based hormone reporter gene assays and increasing fractionation resolution to allow testing of smaller fractions with reduced complexity. The high-resolution EDA approach is demonstrated by analysis of four environmental passive sampler extracts...

Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese...

Objective: Tamoxifen is used as a complementary treatment for estrogen receptor (ER)-positive breast cancer (BCa), but many patients developed resistance. The aim of this study was to examine the role of syndecan-binding protein (SDCBP) silencing in ER-positive BCa cells. Methods: In MCF-7/T47D cells, the effects of SDCBP silence/overexpression on cell proliferation and estrogenic response were examined. Cell proliferation was examined using the MTT assay and cell cycle regulators were examined by Western blot...

Purpose: Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. Results: We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features...

The ovariectomized (OVX) mouse model has been widely accepted to be suitable for the study of postmenopausal osteoporosis. However, whether C57BL/6J mice, a commonly used genetic background mouse strain, is an appropriate model for postmenopausal osteoporosis remains controversial. The present study investigated the effect of the OVX model on alterations in bone density and microarchitecture in C57BL/6J female mice of different ages. C57BL/6J mice were divided into 8-, 12- and 16-week-old groups (OVX8 , OVX12 and OVX16 ) from the beginning of OVX...

Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...

Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small molecule-mediated, selective degradation of dysregulated proteins. We have devised a protein-knockdown system that utilizes chimeric molecules termed specific and nongenetic IAP-dependent protein erasers (SNIPERs) to induce ubiquitylation and proteasomal degradation of various target proteins. SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxy-tamoxifen by a PEG linker, and we have previously reported that this SNIPER efficiently degrades the ERα protein...

Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...

Energy balance and reproductive functions are closely linked in some species. The sex hormones (estrogens and androgens) are involved in the regulation of appetite, metabolism, body weight (BW), and body composition in mammals. Previously, we showed that the effects of testosterone on BW, appetite, and fat weight were markedly affected by alterations to the gonadal hormonal milieu. In this study, we examined whether testosterone administration changes food preferences and whether these effects of testosterone depend on gonadal status in female rats...

Aurora kinase A (Aurora-A), a member of the Aurora family of serine/threonine kinases, plays a critical role in multiple steps of mitotic progression, including microtubule stability during the G1 phase of the cell cycle, chromosome alignment and segregation, and cytokinesis and is aberrantly expressed in various types of human cancers. In addition to its classic functions, recent studies have indicated that Aurora-A is critical for controlling self-renewal of embryonic stem cells through negative regulation of p53...

AIMS: Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. MAIN METHODS: Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected...

Work over the last 15 years on the control of pulsatile LH secretion has focused largely on a set of neurons in the arcuate nucleus (ARC) that contains two stimulatory neuropeptides, critical for fertility in humans (kisspeptin and neurokinin B (NKB)) and the inhibitory endogenous opioid peptide (EOP), dynorphin, and are now known as KNDy (kisspeptin-NKB-dynorphin) neurons. In this review, we consider the role of each of the KNDy peptides in the generation of GnRH pulses and the negative feedback actions of ovarian steroids, with an emphasis on NKB and dynorphin...

Ovarian follicular cell undergoes extensive proliferation and differentiation during the period that the follicle evolved from the primordial state to its ovulatory phase and then corpus luteum status. During this process, different and various levels of steroid hormones in follicular fluid, or obtained from circulation and adjacent cells as granulosa and theca cells, or from environment and diet will all affect the process of follicular growth and development. Differential steroid hormones might have differential effects on ovarian folliculogenesis via the effect on granulosa cell growth and follicular fluid formation that involves cell proliferation, apoptosis, and angiogenesis within the follicle...

The existence of sex differences in digit-length ratio (especially between the second and fourth digits, 2D:4D) is well established for humans from fetal life onwards, and has been linked with later performance. In rodents, the ratio is affected prenatally by exposure to androgens and estrogens, with some research suggesting an influence from sex of the neighbouring intrauterine fetus. However, the ubiquity and ontogenetic development of sexual dimorphism in digit ratios is not well established among wild amniotes...

BACKGROUND: The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. METHODS: We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients...